The in vitro effect of ethanol on membrane structure and transport properties was studied in isolated renal brush border membrane vesicles.31P-NMR studies showed a dose-dependent increase in the quantity of an isotropic, possibly inverted-micellar component of the renal brush-border membrane as a result of treatment with ethanol. Such structures have been shown to be instrumental in the translocation of material across membrane bilayers. A23Na-NMR study of Na+ exchange in artificial phosphatidylcholine liposomes indicated that ethanol (0.1%) was capable of rending the otherwise inert vesicles permeable to sodium, supporting the idea that ethanol may exert its action via a direct effect on the structure of the phospholipid bilayer. In the isolated renal brush-border membrane vesicles, like in the artificial liposomes, amiloride-insensitive pathways of Na+ transport were shown to be markedly activated by ethanol. These results were consistent with the inhibitory effect ethanol had on Na+ gradient-dependent transport systems such as the Na+ gradient-dependent d-glucose transport and Na+/H+ exchange. In conclusion, our results indicate that ethanol exerts its effect on the renal brush-border membrane by causing a structural change in the phospholipid bilayer which activates sodium intake. The inhibitory effect of ethanol on glucose uptake and Na+/H+ exchange is secondary, as a result of the dissipation of the energy-producing Na+ gradient. © 1985 Springer-Verlag.